Foto del docente

Stefano Iotti

Full Professor

Department of Pharmacy and Biotechnology

Academic discipline: BIO/12 Clinical Biochemistry and Molecular Biology

Director of Second Cycle Degree in Health Biology

Curriculum vitae

Stefano Iotti is  Professor of Clinical Biochemistry at the University of Bologna, and since 1990 has contributed to the development of in vivo magnetic resonance spectroscopy both in basic research and in diagnostic applications. In 1987 he gained his master's degree (laurea) in Chemistry at the University of Modena, and a doctorate (dottore di ricerca) in Biochemistry at the University of Bologna in 1994. Between 1992 and 1993, at the Metabolic Magnetic Resonance Research and Computing Center and at the Department of Biochemistry and Biophysics of the University di Pennsylvania, Philadelphia (USA), he collaborated on in vivo research on the role of oxygen in the regulation of oxidative phosphorylation, combining techniques of MR spectroscopy and near-infrared spectroscopy (NIRS). Other scientific contributions, at the ICoCEA laboratory of the CNR in Bologna, have included in vitro synthesis of new anti-sense oligonucleotides and nucleosides, obtaining patents for the latter for use as anti-viral agents.
Formerly the research activity was devoted to the study of molecular interaction between drugs and oligonucleotides, and to the synthesis of L-nucleotides in liquid phase. These studies contributed to elucidate the mechanism by which distamycins binds to the DNA minor groove and to discover that L-thymidine is selectively phosphorylated by thymidine kinase of the herpes simplex virus type 1 and not by the human thymidine kinase.
Then, the research activity moved to the in vivo magnetic resonance spectroscopy (MRS) to study non invasively the metabolic pathways in living tissues. The phosphorus MRS (31P-MRS) was employed to explore in vivo the energetic metabolism functionality of human brain and skeletal muscle both in physiologic and pathologic conditions.
The 31P-MRS studies on the kinetics of the of the Pi signal decay after muscular contraction showed to be related to the mechanisms of Pi transport into mitochondria. This finding put the basis to create a new experimental approach to study directly in vivo the kinetics Pi transport. This allowed to build a model of the mechanism of Pi transport into mitochondria, which in turn leaded to find an impairment of the kinetics of Pi transport in the skeletal muscle of Duchenne/Becker carriers. On the basis of this finding a new non invasive diagnostic test was proposed to disclose the carrier status in relatives of Duchenne/Becker patients, particularly useful when the proband is not available to perform molecular genetic analysis.
The studies of the kinetics of phosphocreatine re-synthesis after muscular exercise contributed to create a non invasive method to assess the functionality of mitochondrial respiration proposing the 31P-MRS as new diagnostic tool for the muscular mitochondrial pathologies.
The further development of the research on the energetic metabolism required the design of a qualitative and quantitative chemical model describing the interactions between the phosphorylated molecules mainly involved in the energetic pathway and the ions present in the cellular environment. This model has been used to build original methods to quantify in vivo by 31P-MRS the cytosolic pH and the free cytosolic [Mg2+] in human brain and skeletal muscle.
In addition a relevant body of the research activity by MRS has been directed to the study of pathogenetic mechanisms and to the therapy effects of several neuronal and neuromuscular diseases.
An other important achievement was reached in the study of the role of oxygen in the regulation of oxidative phosphorylation in skeletal muscle combining near infrared spectroscopy (NIRS) and 31P-MRS, showing that in normoxic conditions the oxygen availability is not limiting the oxidative phosphorylation even at maximal rate of energy requirements.
More recently the research activity has been devoted: i) to the re-definition of the equilibrium constants of phosphorylated metabolites involved in the energetic metabolism taking into account the influence of magnesium measured in vivo by 31P-MR; ii) to the design and development of quantitative mathematical approach for the in vivo assessment of tissue thermodynamics; iii) to the development of an absolute quantification method of the metabolites detectable by proton magnetic resonance spectroscopy (1H-MRS) in order to enlarge the diagnostic value of MRS; iv)to the design and development of new radiofrequency surface coils for MRS equipments with improved sensitivity and spatial selectivity which resulted in two co-authored patents.

At present a significant part of the activity is directed to the study of magnesium homeostasis both in living human tissues by in vivo 31P-MRS and in vitro in cell culture by confocal microscopy and fluorimetric techniques using a new class of fluorescent sensors for Magnesium in Living Cells which are hydroxyquinoline derivatives recently developed whose improved synthesis has been recently patented. This research line exploits the partnership with the Research Centers of APS Argonne (Chicago) and Elettra (Trieste) for Synchrotron X-ray measurements for the Mg2+ intracellular mapping of different lines of tumor cells sensitive and resistant di several anticancer drugs.
Last but not least, in collaboration with prof. Sabatini and Vacca of the University of Florence, a novel procedure was developed to simplify the treatment of the thermodynamics of complex systems. This approach of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions.
The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately, and represents a new paradigm in the biochemical thermodynamics.The author of numerous publications, he regularly acts as a referee for international scientific journals concerned both with the applications of MR spectroscopy and with basic biochemistry.